New use of ammonium compounds and/or urea

ABSTRACT

The use of a physiologically innocuous ammonium compound and/or urea as an additive to an infant formula or a pap or for the preparation of a pharmaceutical composition for the prophylaxis of sudden infant death syndrome (SIDS) is disclosed as is also, an infant formula or a pap which in addition to conventional ingredients contains a physiologically innocuous ammonium compound an/or urea. Furthermore, a method of preventing SIDS is disclosed, which method comprises administering to the infant an infant formula or a pap as indicated above, and a method for prophylaxis of SIDS, wherein a pharmaceutical composition containing a physiologically innocuous ammonium compound and/or urea is administered to the infant or the appropriately selected or modified non-pathogenic, urease-producing bacteria are supplied to the gastrointestinal tract of the infant. Finally, a method for the diagnosis of the risks for SIDS is disclosed according to which method the faeces of the infant are analyzed with respect to the presence of urea, urease activity and/or ammonium ions, the presence of urea, the absence of abnormally low urease activity and ammonium ion, respectively, indicating risks for SIDS.

ANNEX INCLUDING CLEAN VERSION OF AMENDED SPECIFICATION

[0001] Please replace the paragraph beginning at line 5 on page 2 withthe following: In order that an animal or a human being should be ableto live it is required that its body functions are regulated in such away that there is an acid-base balance. Expressed in another way: Anormal pH-value must exist in the cells, in the extracellular liquid andin the cell organelles. If this is not the case first slight functionaldisorders, then even increasing diseases and finally death ofstructures, cells and the whole organism occurs. For instance, it isknown that the mortality in several diseases increases when the pH valueof the extracellular liquid (normally 7.40) is above 7.55 or below 7.20.

[0002] Please replace the paragraph beginning at line 17 on page 2 withthe following: Under the latest decades the opinion of the acid-basebalance has not changed materially. During the 1980's, however, Atkinsonand co-workers [Atkinson D E et al, Curr Top Cell Regul, 21, 261-302(1982)] again called attention to the previously known, but amongphysiologists and medical physicians not accepted fact that themetabolism of mammals not only produced the main metabolites carbondioxide, water and urea but also hydrogen carbonate. His theory alsomeant that the metabolism by producing hydrogen carbonate above all viaamino acid metabolism in order to result in the metabolic end productscarbon dioxide and water must be supplied with protons and that thisprocess for quantitative reasons had to occur via the omithine cycle.One of the objections against this theory has been that if such animportant life process does not function the animal or the human beingin question should rapidly die. However, no such lacking function of thesystem proposed by Atkinson has even been pointed out and even less beenproven which constitutes one of the deficiencies of his theory.

[0003] Please replace the paragraph beginning at line 1 on page 5 withthe following: portal area, especially at acidosis, can be utilized forsynthesis of glutamine in the liver. It is also known by intensive carephysicians that ammonium chloride supplied intravenously and perorallylowers base excess values and such supply is accordingly used as amatter of routine for the treatment of a metabolic alkalosis. When thepatient treated is breathing by himself, the supply of ammonium willbring about a so-called compensatory hyperventilation. The presentinventor has administered himself 80 mmoles ammonium chloride perorallyand thereby has been able to establish that this substance obviously isresorbed very quickly from the gastrointestinal tract and causes aslight hyperventilation which in turn causes an increase in RQ(“Respiratory Quotient”=the quotient between the carbon dioxide emissionand the oxygen gas uptake in a person—in both cases expressed in ml/min)from a value at rest of 0.82 to 0.87 and the elimination of carbondioxide increases by 30 ml/min and that this seems to proceed for nearly1h, which corresponds to about 80 mmoles of carbon dioxide. Furthermore,there is a report on the concentration of urea in the vitreous body ofdead SIDS patients which is compared to autopsy material from childrendeceased from other causes at the same age [Blumenfeld T A, et al, Am JClin Pathol, 71, 219-223 (1979)]. It appeared that children deceasedfrom SIDS have lower urea values than children deceased from othercauses. As a normal enterohepatic circulation of urea and ammonium ionhypothetically does not function in these cases this should have theconsequence that the production of urea is less than normally and sincethe volume of distribution is equal this means that the concentration invarious body fluids decreases. The low concentration of urea found isthus not inconsistent with the hypothesis put forward here.

In the claims:
 11. An infant formula comprising an effective amount ofammonium chloride as an additive to said infant formula, wherein saideffective amount of ammonium chloride is sufficient to reduce the riskof sudden infant death syndrome (SIDS) in infants.
 12. The infantformula of claim 11, wherein the ammonium chloride is present at aconcentration of 0.2-0.6 mmol/l in an infant formula ready foradministration to an infant during the first month of life.
 13. Theinfant formula of claim 11, wherein the ammonium chloride is present ata concentration of 0.1-5 mmol/l in an infant formula ready foradministration to an infant during months 2-7 of life.
 14. The infantformula of claim 11, which is in the form of a powder.
 15. The infantformula of claim 12, wherein the concentration of the ammonium chlorideis 0.5 mmol/l.
 16. The infant formula of claim 12, wherein theconcentration of the ammonium chloride is 0.5-2 mmol/l.
 17. A method ofreducing the risk of sudden infant death syndrome (SIDS) in infantscomprising administering an infant formula or pap composition comprisingan effective amount of ammonium chloride, urea or a mixture thereof,wherein said effective amount of ammonium chloride, urea or mixturethereof is sufficient to reduce the risk of SIDS in infants.
 18. Themethod of claim 17, wherein the infant formula or pap composition isadministered to an infant during the first month of life, and theconcentration of ammonium chloride in the infant formula or papcomposition is 0.2-0.6 mmol/l.
 19. The method of claim 17, wherein theinfant formula or pap composition is administered to an infant duringmonths 2-7 of life, and the concentration of ammonium chloride in theinfant formula or pap composition is 0.1-5 mmol/l.
 20. The method ofclaim 17, wherein the infant formula or pap composition is administeredto an infant during the first month of life, and the concentration ofurea in the infant formula or pap composition is 1-5 mmol/l.
 21. Themethod of claim 17, wherein the infant formula or pap composition isadministered to an infant during months 2-7 of life, and theconcentration of urea in the infant formula or pap composition is 1-10mmol/l.
 22. A method for the prophylaxis of sudden infant death syndrome(SIDS) in infants comprising administering an infant formula or papcomposition comprising an effective amount of ammonium chloride, urea ormixture thereof wherein said effective amount of ammonium chloride, ureaor mixture thereof is sufficient for prophylaxis of SIDS in infants. 23.The method of claim 22, wherein the infant formula or pap composition isadministered to an infant during the first month of life, and theconcentration of ammonium chloride in the infant formula or papcomposition is 0.2-0.6 mmol/l.
 24. The method of claim 22, wherein theinfant formula or pap composition is administered to an infant duringmonths 2-7 of life, and the concentration of ammonium chloride in theinfant formula or pap composition is 0.1-5 mmol/l.
 25. The method ofclaim 22, wherein the infant formula or pap composition is administeredto an infant during the first month of life, and the concentration ofurea in the infant formula or pap composition is 1-5 mmol/l.
 26. Themethod of claim 22, wherein the infant formula or pap composition isadministered to an infant during months 2-7 of life, and theconcentration of urea in the infant formula or pap composition is 1-10mmol/l.
 27. A pap composition comprising an effective amount of ammoniumchloride as an additive to said pap composition, wherein said effectiveamount of ammonium chloride is sufficient to reduce the risk of suddeninfant death syndrome in infants.
 28. The pap composition of claim 27,wherein the ammonium chloride is present at a concentration of 0.1-5mmol/l in an infant formula ready for administration to an infant duringmonths 2-7 of life.
 29. The pap composition of claim 27, which is in theform of a powder.
 30. The pap composition of claim 28, wherein theconcentration of the ammonium chloride is 0.5 mmol/l.
 31. The papcomposition of claim 28, wherein the concentration of the ammoniumchloride is 0.5-2 mmol/l.